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METASTASIS

Radiation sparks a dark side in neutrophils

Nature Cancer volume 3, pages 136–137 (2022)Cite this article

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Neutrophils may obtain either pro- or anti-tumorigenic phenotypes depending on environmental cues. A new study reports that cancer radiotherapy induces a neutrophilic response associated with tissue repair and leads to enhanced metastatic spread, highlighting a mechanism by which neutrophils promote metastatic tumor growth.

Neutrophils are the most abundant white blood cells in the human circulation and were traditionally associated with fighting infection and promoting inflammation. In recent years, neutrophils have also been attributed unconventional roles in the context of cancer. They have been shown to promote tumor growth by increasing angiogenesis, providing pro-tumorigenic cytokines, mediating immune evasion and modulating the extracellular matrix. Furthermore, neutrophils have been identified as enhancers of metastatic spread by promoting intravasation at the primary site, priming the pre-metastatic niche and releasing neutrophil extracellular traps (NETs)1. By contrast, neutrophils exert an anti-tumorigenic role via direct anti-tumor cytotoxicity or the activation of other immune responses2,3. These opposing roles of neutrophils probably stem from the fact that they are a heterogeneous population of cells4, and their function is ultimately determined by signals derived from the microenvironment5. Still, because neutrophils, as a major component of the immune system, are expected to protect the host from cancerous events, the fact that they promote tumor growth and metastatic progression may sound counterintuitive. However, in most cases, the pro-tumor activity of neutrophils is actually the hijacking of a ‘normal’ response to injury to benefit the growing tumor. A prime example of this is neutrophil-mediated enhancement of angiogenesis at the primary tumor site. Once a fast-growing tumor has nutrient requirements that exceed available resources, factors emanating from the hypoxic environment drive neutrophils towards providing pro-angiogenic signals to help to alleviate poor tumor perfusion. This ‘physiological’ neutrophil response facilitates tumor growth and metastasis6.

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Fig. 1: Irradiation stimulates a neutrophilic response that leads to enhanced metastatic propensity.

Amina Jbara.

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  1. Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University Medical School, Jerusalem, Israel

    Adina Heinberg & Zvi Granot

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  1. Adina Heinberg
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  2. Zvi Granot
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Correspondence to Zvi Granot.

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Heinberg, A., Granot, Z. Radiation sparks a dark side in neutrophils. Nat Cancer 3, 136–137 (2022). https://doi.org/10.1038/s43018-021-00324-3

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  • DOI: https://doi.org/10.1038/s43018-021-00324-3

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